4.1 Interventions to raise haemoglobin levels in patients with malignancies

4.1.2 Tumour hypoxia and radiotherapy resistance

High-energy photons used in radiotherapy induce deoxyribonucleic acid (DNA) damage. The photons can either directly cause electrons to ionize DNA helix atoms, or can produce highly reactive free radical species, which then interact with and damage DNA. Unrepaired DNA damage inhibits cell proliferation and leads to cell death. The presence of oxygen contributes to the indirect process by prolonging the life span of the free radicals. Oxygen also decreases the ability of cells to repair DNA damage, so that well-oxygenated cells are more radiosensitive than hypoxic cells.

Hypoxia may also contribute to tumour radiation resistance. This can be caused by altered cell proliferation kinetics, reduction of apoptosis and differentiation, and reduced cell growth associated with slowed protein synthesis. Hypoxia may also increase malignant progression and aggressiveness through clonal selection and genome changes, with an adverse effect on patient outcomes.